Sterilization method

ABSTRACT

A method of sterilizing a material, said method comprising the steps of: a) providing a sterilizing composition comprising (i) peracetic acid and (ii) a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid and propane-1,2,3-tricarboxylic acid; b) introducing such sterilizing composition into a hot gaseous stream to produce a peracetic acid vapor; and c) contacting such peracetic acid vapor with the material to be sterilized. The use of such an organic acid stabilizer results in an unexpected reduction in the amount of residue deposited on the heating surface employed to vaporize the sterilizing composition.

FIELD OF THE INVENTION

The present invention is directed to a method of sterilizing a material, said method comprising the steps of: a) providing a sterilizing composition comprising (i) peracetic acid and (ii) a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid and propane-1,2,3-tricarboxylic acid; b) introducing such sterilizing composition into a hot gaseous stream to produce a peracetic acid vapor; and c) contacting such peracetic acid vapor with the material to be sterilized. The use of such an organic acid stabilizer results in an unexpected reduction in the amount of residue deposited on the heating surface employed to vaporize the sterilizing mixture.

BACKGROUND OF THE INVENTION

The necessity of sterilizing surfaces for health and sanitary purposes has long been recognized. Effective sterilization processes are needed for a variety of purposes including aseptic packaging, medical instrument sterilization, biocidal vector environmental remediation, fumigation, vessel sterilization, food stuff treatments, and others.

Among the compounds employed as a sterilizer for such uses is peracetic acid (“PAA”), also called peroxyacetic acid. In order to prolong the shelf-life of PAA compositions, stabilizers are typically added. These stabilizers act as chelators for dissolved metal cations that can disrupt the peroxide bond.

The use of vapor phase peracetic acid to sterilize surfaces is described in US Patent Application 2010/0196197. This publication discloses the use of peracetic acid stabilized with phosphonic acid or acid stabilizers such as Dequest 2010, 1-Hydroxyethylidene-1,1,-diphosphonic acid. While such process is effective to sterilize a variety of different surfaces, it has been found that when such phosphonic acid stabilizers are employed the surface of the heating element used to vaporize the peracetic acid solution tends to become covered with residue over a period of time. This build-up of residue requires that such surface be periodically cleaned, a process which can be time consuming and expensive.

It would therefore be highly desirable to possess a method for using vapor phase peroxyacetic acid as a sterilizing agent which method did not require the relatively frequent cleaning of the heating surfaces of the equipment employed.

While PAA compositions comprising citric acid have been disclosed in the past, such compositions have been employed in liquid aqueous sanitizing applications only. Thus, for example, WO 2008/079999 discloses sterilizing compositions comprised of PAA, citric acid or a salt thereof, and salicylic acid or a salt thereof, which compositions are applied topically to the surfaces to be disinfected employing solution spray systems or the like. Somewhat similarly, U.S. Pat. No. 6,117,457 and European Patent Application 720814 both disclose the use of citric acid in aqueous PAA generation systems; either as a pH regulator in fish ponds or as a means of providing extended PAA generation, respectively.

However, it has now been unexpectedly found that when PAA stabilized with an organic acid such as citric acid is employed in vapor phase sterilization, the buildup of residue on heating surfaces is considerably less than when a phosphonic acid stabilizer is employed. This result is particularly unexpected in view of the showing that aqueous solutions of citric acid (in the absence of PAA) result in the undesirable buildup of residue on heating surfaces.

SUMMARY OF THE INVENTION

The present invention is directed to a method of sterilizing a material, said method comprising the steps of: a) providing a sterilizing composition comprising (i) peracetic acid and (ii) a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid and propane-1,2,3-tricarboxylic acid; b) introducing such sterilizing composition into a hot gaseous stream to produce a peracetic acid vapor; and c) contacting such peracetic acid vapor with the material to be sterilized.

This method permits the effective vapor sterilization of a material without the need for frequently disassembling the apparatus employed in order to remove the buildup of residue which occurs upon the heating surfaces of such apparatus. Accordingly, a wide variety of materials may be rapidly and economically sterilized employing the method of this invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to a method of sterilizing a material, said method comprising the steps of: a) providing a sterilizing composition comprising (i) peracetic acid and (ii) a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid and propane-1,2,3-tricarboxylic acid; b) introducing such sterilizing composition into a hot gaseous stream to produce a peracetic acid vapor; and c) contacting such peracetic acid vapor with the material to be sterilized.

As is employed herein, the term vapor means a state in which the peracetic acid is substantially entirely in the gaseous form. This is in contrast to mist or fog, both of which contain a significant proportion of liquid droplets suspended in the air. Unlike the use of a mist or fog, it has been found that the use of peracetic acid in vapor form provides excellent sterilization of materials without the concomitant formation of water droplets on the material surface.

Peracetic acid is typically employed in the form of an aqueous equilibrium mixture of acetic acid, hydrogen peroxide and peracetic acid. The weight ratios of these components may vary greatly, depending upon the particular grade of PAA employed. Among the grades of PAA which may be employed are those having weight ratios of PAA:hydrogen peroxide:acetic acid of from 12-18:21-24:5-20; 15:10:36; 5:23:10; and 35:10:15.

The stabilizer employed in the PAA sterilizing composition is selected from the group consisting of citric acid, isocitric acid, aconitic acid and propane-1,2,3-tricarboxylic acid. Preferably, such stabilizer is citric acid.

Typically, the stabilizer is employed in an amount sufficient to stabilize the PAA for at least three months. Preferably, the stabilizer is present at a concentration sufficient to stabilize the PAA for a period of at least six months.

In general, such stabilizer will typically be present in an amount of between about 0.75% and about 1.5%; preferably of between about 0.9% and 1.25%; and more preferably of between about 1.0% and about 1.2%; all such percentages being by weight, based upon the total weight of the PAA composition.

The composition employed in the process of this invention may further comprise sequestriants such as dipicolinic acid, as well as other ingredients such as mineral acid catalysts (sulfuric, nitric, or phosphoric acids); surfactants such as anionic laurylates, sorbitans and their respective esters, i.e. polyethylene sorbitan monolaurylates; and short chain fatty esters (C6-C12) forming mixed peracids in solution.

In addition, the compositions employed in the process of this invention may further comprise one or more additional oxidants selected from the group consisting of chloroperbenzoic acid, perheptanoic acid, peroctanoic acid, perdecanoic acid, performic acid, percitric acid, perglycolic acid, perlactic acid and perbenzoic acid.

In the practice of the process of this invention, the peracetic acid sterilizing composition is preferably diluted, prior to its introduction into the heated gas stream, by the addition of high quality water (deionized water with ≥2 MOhm resistivity or ≤0.5 μSiemens conductivity), to a concentration of less than about 10,000 parts per million (ppm) of PAA, preferably to a concentration of less than about 4,000 ppm PAA.

The heated gas stream is typically sterile air, although other gases such as nitrogen, CO₂, or inert noble gas carriers may also be employed. Such gas stream is typically heated to a temperature of at least about 300° C., preferably to a minimal temperature of about 250° C. and can be in excess of 350° C. providing it can be cooled sufficiently for application. It then is typically cooled to between about 80° C. and about 120° C. prior to the introduction of the peracetic acid solution. The heated gas stream at the point of peracetic acid introduction should have a temperature of at least 5° C. higher than the dew point of peracetic acid (ca. 46.5°-49.9° C.); i.e., of at least about 55° C., in order to ensure that the peracetic acid is converted into a vapor rather than a fog or mist.

The peracetic acid may be introduced into the heated air stream by any means well known to one of skill in the art. One preferred method is by direct injection of a solution.

The peracetic acid vapor is then contacted with the material to be sterilized for a period sufficient to kill the contaminants of concern. This time period will vary according to variables such as the concentration of the peracetic acid vapor employed; the nature of the surface of the material to be sterilized; the particular contaminants to be sterilized; the concentration of the contaminants to be sterilized; and the like. Typically, such contact will maintained for a period of between about 15 and about 40 minutes.

A wide variety of materials may be sterilized employing the method of this invention, including hard surfaces of metals, plastics, polymers, and elastomers.

The present method may be used to sterilize materials contaminated with those bacteria typically controlled by peracetic acid in the liquid form. These include bacteria and spores of the genus Bacillus using B. thuringiensis and B. atrophaeus as surrogates for more pathogenic species (forms) such as C. botulinum as well as more typical genera of bacteria, fungi, and viruses and protozoans often controlled by PAA such as (but not limited to): Staphylococcus, Enterococcus, Salmonella, Campylobacter, Pseudomonas, Candida, Rhizopus, Mucor, Influenza, Bacilli, etc.

The following Examples are presented to offer further illustration of the present invention, but are not intended to limit the scope of the invention in any manner whatsoever.

Example 1

In order to demonstrate the stabilizing effect of citric acid on PAA compositions, varying amounts of citric acid were added to concentrated PAA compositions, which compositions were stored at room temperature. Periodically, at the times indicated in Tables 1-4 below, samples of such compositions were analyzed for their peracetic acid (PAA); hydrogen peroxide (H₂O₂); and acetic acid (AA) contents (in percent by weight); and their Active Oxygen Recovery percentage (AO Rec) was calculated. The data presented in such Tables indicates that citric acid alone can stabilize PAA compositions for extended periods of more than 3 or 6 months.

TABLE 1 0.91% Citric Acid Days After AO Addition PAA % H₂O₂ % AA % Rec % — 0.8438 15.0778 49.4288 88.94 1 2.8207 14.4139 47.1477 90.21 2 4.8579 13.7938 45.1340 91.89 3 6.8554 13.1946 43.4419 93.58 4 8.1230 12.7316 42.2202 94.18 8 12.1365 11.4882 38.1054 97.35 9 11.8892 11.2862 37.8752 95.55 10 12.8904 11.1100 37.6596 97.12 11 13.3851 11.0106 36.8579 97.82 14 15.3285 10.6744 35.9054 100.89 15 14.4656 10.6141 35.8921 98.32 16 14.7712 10.5483 36.6383 98.72 17 15.4082 10.5003 36.1812 100.09 18 15.0226 10.4909 36.6624 99.04 21 15.3530 10.3126 35.4124 98.87 28 16.1285 10.1703 34.9291 100.04 36 16.0191 10.0980 34.7712 99.35 43 16.6856 10.0932 34.0215 101.03 77 15.7208 9.8166 35.5012 96.96 95 15.8097 9.8772 35.7577 97.54 133 15.4084 9.7041 35.5974 95.51 162 14.2637 9.6438 36.2839 92.21 197 14.8616 9.5118 35.3907 92.99 228 14.5168 9.4222 35.9890 91.59 260 13.9939 9.2273 36.6908 89.12 285 13.8226 9.1102 36.1968 88.01 314 14.2674 9.0070 36.6037 88.56 344 13.3877 8.9848 36.4208 86.17 378 13.5115 8.8263 36.9739 85.57 403 13.0327 8.6849 37.7293 83.53

TABLE 2 1.00% Citric Acid Days After AO Addition PAA % H₂O₂ % AA % Rec % — 0.8688 17.1802 47.8195 101.08 1 2.8990 15.7369 45.8501 98.00 2 5.1241 14.8095 43.8144 98.39 3 7.1400 13.9885 42.6610 98.86 4 8.4730 13.3357 41.1202 98.53 8 12.0610 11.7606 37.6254 98.70 9 12.8241 11.5194 37.3773 99.28 10 13.1537 11.3034 37.6218 98.88 11 13.3192 11.1213 37.4239 98.26 14 14.8345 10.7323 36.7059 99.92 15 14.8165 10.6578 36.3016 99.45 16 14.8555 10.5471 35.7440 98.91 17 14.9233 10.5083 36.4307 98.86 18 15.1771 10.4201 35.2700 99.01 21 15.5752 10.2907 35.7839 99.29 28 16.0195 10.1210 34.7292 99.45 36 15.4584 10.0619 35.0277 97.67 43 15.9848 10.0408 34.6613 98.90 77 15.6363 9.8988 35.8995 97.19 95 15.4839 9.8409 34.7765 96.46 133 15.0663 9.6691 36.3532 94.40 162 14.8545 9.6176 36.6276 93.56 197 14.8315 9.477 35.6838 92.69 228 14.4704 9.3548 36.0888 91.06 260 15.0582 9.2067 35.5108 91.72 285 14.3021 9.0621 36.2798 88.94 314 14.197 8.956 37.3694 88.06 344 13.9533 8.8917 36.8442 87.06 378 13.1943 8.7715 37.5735 84.42 403 12.9297 8.6296 37.1723 92.82

TABLE 3 1.15% Citric Acid Days After AO Addition PAA % H₂O₂ % AA % Rec % — 0.9493 14.9203 49.7722 88.31 1 2.7103 14.0927 47.8537 88.08 2 4.8674 13.5088 45.8163 90.27 3 6.7840 12.8510 44.2981 91.42 4 8.0746 12.4248 42.6000 92.29 8 11.8005 11.2592 38.8622 95.17 9 12.7506 11.1215 37.9775 96.82 10 13.0775 10.9839 37.7389 96.87 11 13.7122 10.8617 38.0374 97.80 14 14.4521 10.6744 36.8023 98.63 15 14.7832 10.5997 36.0188 99.05 16 14.9035 10.5517 35.5883 99.09 17 14.9890 10.5392 35.5743 99.23 18 15.1184 10.4180 35.4307 98.87 21 15.7941 10.3115 35.4520 100.00 28 16.1877 10.1272 34.7089 99.95 36 15.0727 10.0837 34.9070 96.83 43 15.8094 10.0461 35.0496 98.51 77 15.5986 9.8953 35.6593 97.10 95 15.5719 9.8333 35.9455 96.67 133 16.0577 9.6417 34.8538 96.82 162 15.1268 9.5816 36.0882 94.08 197 15.7167 9.5183 34.8321 95.23 228 13.9662 9.3003 36.2149 89.47 260 13.4297 9.1271 36.3155 87.09 285 14.3050 9.0125 36.4291 88.69 314 13.5222 8.9160 36.6740 86.12 344 13.8437 8.8414 37.2805 86.51 378 13.0769 8.7360 47.0423 83.93 403 12.9157 8.5879 37.2918 82.67

TABLE 4 1.24% Citric Acid Days After AO Addition PAA % H₂O₂ % AA % Rec % — 0.7259 12.9350 51.4255 76.31 1 2.6857 13.1213 48.8097 82.42 2 4.7080 12.8994 46.6388 86.35 3 6.6668 12.4803 45.0566 88.98 4 8.1618 12.0665 43.2028 90.45 8 12.3648 11.1363 39.9843 95.91 9 12.5204 10.9715 38.9763 95.37 10 13.1867 10.8514 38.4447 96.39 11 13.8380 10.7723 37.6754 97.61 14 14.3456 10.5460 36.8458 97.62 15 14.6369 10.5380 36.0910 98.32 16 14.7992 10.4648 35.8426 98.43 17 14.9864 10.4538 35.7862 98.74 18 15.3825 10.4189 36.6292 99.55 21 15.3706 10.2649 35.4215 98.64 28 15.8088 10.1306 35.0317 98.99 36 15.8843 10.0424 35.1196 98.68 43 15.9236 10.0629 35.2217 98.90 77 15.6937 9.8773 35.6800 97.24 95 15.7823 9.7861 36.1936 96.94 133 15.1511 9.6406 35.6101 94.48 162 15.0181 9.5280 36.4564 94.39 197 15.5437 9.3555 35.0428 93.85 228 14.1509 9.2284 36.2681 89.53 260 14.9844 9.0772 35.7010 90.81 285 14.3708 8.9362 36.5596 88.42 314 14.1109 8.7402 36.4426 86.62 344 13.9393 8.7677 36.9396 86.34 378 13.4533 8.6343 37.2074 84.32 403 13.3214 8.5447 38.2168 83.46

Example 2

In order to determine the amount of residue buildup produced by vaporization, various solutions were prepared by blending the following ingredients:

Samples A1, A2 and A3: 250 ppm citric acid in deionized water

Sample B1: 4000 ppm PAA+about 24 ppm Dequest 2010

Samples C1 and C2: 4000 ppm PAA+250 ppm citric acid

The PAA employed had a PAA:hydrogen peroxide:acetic acid weight ratio of about 15:10:36.

An initial portion of the sample to be tested was placed into a 50 mL burette suspended over a 100 mL beaker placed on a Corning Stirrer/Hotplate. The hotplate was heated to 180° C. and the stopcock on the burette opened such that the solution was added drop wise for vaporization. The burette was refilled before it ran out of solution. The hotplate was shut off and the beaker allowed to return to room temperature. Once it had cooled to room temperature, the beaker was reweighed to determine the amount of residue present. The results observed and the calculated amount of residue (mg/mL) are summarized in Table 5 below.

TABLE 5 Residue Volume of Mg/mL Sample (mg) Solution (mL) of Residue A1 20 92.5 0.22 A2 31 109.9 0.28 A3 27 117 0.23 B1 131 94.3 1.39 C1 0 121.6 0.00 C2 3 92 0.03

The above results show that the method of the present invention (exemplified in Samples C1 and C2) produces considerably less residue of the heating surface than does a PAA composition of equal concentration which is stabilized using a phosphonate stabilizer. This result is completely unexpected in view of the showing that the vaporization of citric acid in deionized water results in the formation of a much more residue than does the vaporization of a composition comprising an equal amount of citric acid in a PAA solution. 

What is claimed is:
 1. A method of sterilizing a material, said method comprising the steps of: a) providing a sterilizing composition comprising (i) peracetic acid and (ii) a stabilizer selected from the group consisting of citric acid, isocitric acid, aconitic acid and propane-1,2,3-tricarboxylic acid; b) introducing such sterilizing composition into a hot gaseous stream to produce a peracetic acid vapor; and c) contacting such peracetic acid vapor with the material to be sterilized.
 2. The method of claim 1 wherein the peracetic acid is present in a concentration of from about 15 to about 17 weight percent of the sterilizing composition; and the stabilizer is present in an amount between about 0.75 and about 1.5 weight percent of the sterilizing composition.
 3. The method of claim 2 wherein the stabilizer is present in an amount between about 0.9 and about 1.25 weight percent of the sterilizing composition.
 4. The method of claim 3 wherein the stabilizer is present in an amount between about 1.0 and about 1.2 weight percent of the sterilizing composition.
 5. The method of claim 1 wherein the stabilizer is citric acid.
 6. The method of claim 2 wherein the stabilizer is citric acid.
 7. The method of claim 3 wherein the stabilizer is citric acid.
 8. The method of claim 4 wherein the stabilizer is citric acid.
 9. The method of claim 1 wherein the material is selected from the group consisting of metals, plastics, polymers and elastomers.
 10. The method of claim 1 wherein the peracetic acid is diluted to a concentration of less than 10,000 ppm prior to being introduced into the hot gaseous stream.
 11. The method of claim 10 wherein the peracetic acid is diluted to a concentration of less than 4,000 ppm prior to being introduced into the hot gaseous stream.
 12. The method of claim 1 wherein the hot gaseous stream is sterile air.
 13. The method of claim 1 wherein the hot gaseous stream is selected from the group consisting of nitrogen, carbon dioxide and noble gases.
 14. The method of claim 1 wherein the hot gaseous stream is heated to a temperature above about 250° C. prior to the introduction of the peracetic acid.
 15. The method of claim 1 wherein the hot gaseous stream is heated to a temperature above about 250° C. and is then cooled to a temperature of between about 80° C. and about 120° C. prior to the introduction of the peracetic acid.
 16. The method of claim 1 wherein the temperature of the hot gaseous stream is at least about 5° C. higher than the dew point of peracetic acid.
 17. The method of claim 1 wherein the contact between the peracetic acid vapor and the material to be sterilized is maintained for a period of between about 15 and about 40 minutes.
 18. The process of claim 1 wherein the sterilizing composition further comprises one or more additional oxidants selected from the group consisting of chloroperbenzoic acid, perheptanoic acid, peroctanoic acid, perdecanoic acid, performic acid, percitric acid, perglycolic acid, perlactic acid and perbenzoic acid.
 19. The process of claim 1 wherein the PAA is in the form of an aqueous equilibrium composition having a PAA:hydrogen peroxide:acetic acid weight ratio selected from the group consisting of 12-18:21-24:5-20; 15:10:36; 5:23:10; and 35:10:15. 